The application of 3D bioprinting in urological diseases

Abstract

Urologic diseases are commonly diagnosed health problems affecting people around the world. More than 26 million people suffer from urologic diseases and the annual expenditure was more than 11 billion US dollars. The urologic cancers, like bladder cancer, prostate cancer and kidney cancer are always the leading causes of death worldwide, which account for approximately 22% and 10% of the new cancer cases and death, respectively. Organ transplantation is one of the major clinical treatments for urological diseases like end-stage renal disease and urethral stricture, albeit strongly limited by the availability of matching donor organs. Tissue engineering has been recognized as a highly promising strategy to solve the problems of organ donor shortage by the fabrication of artificial organs/tissue. This includes the prospective technology of three-dimensional (3D) bioprinting, which has been adapted to various cell types and biomaterials to replicate the heterogeneity of urological organs for the investigation of organ transplantation and disease progression. This review discusses various types of 3D bioprinting methodologies and commonly used biomaterials for urological diseases. The literature shows that advances in this field toward the development of functional urological organs or disease models have progressively increased. Although numerous challenges still need to be tackled, like the technical difficulties of replicating the heterogeneity of urologic organs and the limited biomaterial choices to recapitulate the complicated extracellular matrix components, it has been proved by numerous studies that 3D bioprinting has the potential to fabricate functional urological organs for clinical transplantation and in vitro disease models.

Keywords: Kidney regeneration; Tissue engineering; Tumor microenvironment; Urethral replacement; Urological cancer.

Graphical abstract

Fig. 1

Tissue engineering and three-dimensional (3D) bioprinting technologies for urological diseases.

Fig. 2

3D bioprinting technologies and comparisons. (a) Extrsusion-based bioprinting; (b) Inkjet-based bioprinting; (c, d) Light-assisted bioprinting.

Fig. 3

Bioprinting for kidney regeneration. (a) 3D printing to pattern human embryonic kidney cells and ovine mesenchymal stem cells in high droplet resolution of 1 ​nL. Adapted with permission [85]. Copyright 2017 Springer Nature (open access); (b) Vascularized proximal tubule using extrusion-based 3D printing. Adapted with permission [103]. Copyright 2017 Frontiers (open access); (c) Micro fluidic bioprinting created core-shell tubes to mimic convoluted proximal tubule. Adapted with permission [120]. Copyright 2020 Elsevier.

Fig. 4

Bioprinting for urethra replacement. (a) Multilayered tubular construction using multichannel coaxial extrusion system. Adapted with permission [104]. Copyright 2018 Wiley; (b) Cell-laden urethra built with PCL/PLCL and fibrin-based hydrogel. Adapted with permission [127]. Copyright 2017 Elsevier; (c) 3D printed PLGA/PCL/TEC tubular structure. Adapted with permission [145]. Copyright 2020 American Chemical Society.

Fig. 5

The application of 3D bioprinting in mimicking PCa TME. (a) Combining 3D printing extrusion system with a rotating structure to prepare a hollow tube that mimics bone structure. Adapted with permission [175]. Copyright 2014 Elsevier; (b) Hollow tube coating with a layer of calcium phosphate to better mimic the chemical properties of human bone and enhance the cell adhesion. Adapted with permission [176]. Copyright 2019 Elsevier; (c) 3D electrowritten scaffolds to prepare an engineered bone microenvironment. Adapted with permission [128]. Copyright 2019 Springer Nature.

Fig. 6

The application of 3D bioprinting in mimicking kidney TME. (a) Bioprinting develops a tunneling nanotube (TNT)-like structure. Adapted with permission [86]. Copyright 2021 Elsevier; (b) Microfluidic devices for circulating tumor cells (CTCs) isolation. Adapted with permission [178]. Copyright 2020 Elsevier.

Fig. 7

The application of 3D bioprinting in mimicking bladder cancer TME. (a) Bioprinted grid structure containing bladder cancer cells to evaluate metastasis. Adapted with permission [105]. Copyright 2019 Public Library of Science; (b) Immune cells and bladder cancer cells co-culture system built with acoustic droplet printing. Adapted with permission [180]. Copyright 2021 Wiley; (c) Bladder cancer-on-a-chip developed with bioprinting and microfluidic technology. Adapted with permission [106]. Copyright 2021 MDPI.

Fig. 8

The development of 3D bioprinting in urological diseases needs the cooperation of printing technics, structure design, biomaterials, engineered cells, and growth factors.